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Experimental and mathematical studies in immunology have revealed that the dynamics

Experimental and mathematical studies in immunology have revealed that the dynamics of the programmed T cell response to vigorous infection can be conveniently modelled using a sigmoidal or a discontinuous immune response function. structure control theory provides a new framework for evaluating immunological dynamics and experimental observations. A modelling and simulation tool results with predictive capacity to determine how to modify the immune response to achieve healthy outcomes which may have application in drug development and vaccine design. Introduction This paper considers the extent to which variable structure control theory can be used to underpin the development of a modelling and simulation tool to analyse and buy 24699-16-9 tailor the dynamics of the specific immune response of T cells post infection. A Variable Structure Control System (VSCS) is a feedback system where the dynamic structure is changed to achieve performance requirements [1]. Switching between different dynamics is advantageous because the desirable properties of several subsystems can be combined so that the overall system possesses new and enhanced dynamical behaviour H3 including properties that are not present in any of the individual subsystems alone. In particular, such VSCS are known to possess strong robustness properties in the presence of parameter uncertainty and disturbances [1, 2]. The theory of VSCS has been applied successfully to mechanical, electrical and chemical systems in the domain of engineering [1, 2]. Understanding of the quantitative and qualitative characteristics of the antigen-specific T cell response is important in immunology [3, buy 24699-16-9 4]. An objective of this paper is to demonstrate the synergies between immunological dynamics and VSCS in order to deliver a new and constructive framework to assess the dynamics of health and disease. The population of T lymphocytes consists of millions of clones characterized by their unique T cell receptor binding with antigen [5]. Each T cell clone is usually activated following the presentation of buy 24699-16-9 a specific antigen by Antigen Presenting Cells (APCs). The theory of the clonal expansion from [6] postulates that antigen-specific immune responses are produced by the proliferation of a small number of antigen-specific cells to a population sufficiently large to influence the progression of the specific pathogen. A number of practical studies have supported this postulate [3C5] because signals produced following interactions with self or foreign tissues induce variation in the behaviour and population dynamics of different immune cells and antibodies [4, 7, 8]. Experiments have demonstrated that after the recognition of bacteria, virus or infected cells, the antigen-specific response of T cells such as CD8+ T cells consists of three phases [7, 9, 10]. The activated T cell clones first exhibit expansion of their initial population so as to combat the pathogen. Next, the resultant large number of antigen-specific T cells undergoes contraction i.e cell death via apoptosis. Finally, the memory phase of the response consists of the differentiation of activated antigen-specific T cells into memory T cells [5]. Hence, the dynamics of the T cell response changes over a relatively short time (days) to induce variations in the population of the specific T cell clones so as to influence the performance of the immune system [4, 6, 9, 11]. Experimental data on the kinetics of the T cell response to different pathogens show two types of expansion dynamic [3, 9, 11, 12]. In some cases, the proliferation of activated T cells monitors and follows the concentration of pathogen [13, 14]. In other cases, an antigen independent expansion dynamic in which the proliferation of activated T cells continues after the infection is cleared is observed [7, 9, 15]. A linear, a Michaelis-Menten, a sigmoidal and a step-like immune response function have been constructed to buy 24699-16-9 model and investigate the antigen dependent expansion phase [16, 17]. The antigen independent expansion phase is often encompassed in a time based on/off immune response function leading to a piecewise linear system [7, 18, 19]. The effects of these candidate immune response functions have been reviewed from a system immunology perspective [3, 9, 12] and from a control engineering view-point in [20]. It has been deduced that the immune response function.